tbuckley/cabot-search huggingface dataset:
Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody
Authors: Behnaz Heydarchi, Danielle S. Fong, Hongmei Gao, Natalia A. Salazar-Quiroz, Jack M. Edwards, Christopher A. Gonelli, Samantha Grimley, Turgut E. Aktepe, Charlene Mackenzie, William J. Wales, Marit J. van Gils, Albert Cupo, Isabelle Rouiller, Paul R. Gooley, John P. Moore, Rogier W. Sanders, David Montefiori, Ashish Sethi, Damian F.J. Purcell
Journal: Cell Reports Medicine (2022)

Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than a majority of CD4bs bNAbs isolated so far. MEL-1872 mAb with CDRH3 of 57 amino acids shows more potency (geometric mean half-maximal inhibitory concentration [IC50]: 0.009 μg/mL; breadth: 66%) than VRC01 against clade B viruses (29-fold) and than CHO1-31 against tested clade A viruses (21-fold). It also shows more breadth and potency than NC-Cow1, the only other reported anti-HIV-1 bovine bNAb, which has 60% breadth with geometric mean IC50 of 0.090 μg/mL in this study. Using successive different stable-structured SOSIP trimers in bovines can elicit bNAbs focusing on epitopes ubiquitous across subtypes. Furthermore, the cross-clade selection strategy also results in ultra-potent bNAbs.
Three-fold Increased Risk of Death in Budd-Chiari Syndrome Compared to Matched Controls: A Population-based Cohort Study
Authors: Fredrik Åberg, Rupesh Rajani, Axel Wester, Linnea Widman, Hannes Hagström
Journal: Clinical Gastroenterology and Hepatology (2022)

Patients with Budd-Chiari syndrome (BCS) have an elevated risk of overall and liver-specific mortality, but this has not been quantified on a population level nor compared against a matched general population cohort.We identified all patients in Sweden with a recorded diagnosis of BCS in the Swedish National Patient Register between 1987 and 2016. Patients with BCS were matched for age, sex, and municipality at baseline with up to 10 reference individuals from the general population. Data on cause-specific mortality were obtained from the Causes of Death Register. A Cox regression model was performed to investigate rates of all-cause and cause-specific mortality.A total of 478 patients with BCS were matched with 4603 reference individuals. Of the patients with BCS, 43% were men, the median age was 58 years, 39% had a recorded diagnosis of a precipitating risk factor, and 13% had underlying liver disease. During a follow-up of up to 29 years, 243 (51%) of the patients with BCS died compared with 1346 (29%) of the reference individuals. Overall mortality was 70 per 1000 person-years in patients with BCS compared with 28 per 1000 person-years in reference individuals, translating into an adjusted hazard ratio (aHR) of 3.1 (95% confidence interval [CI], 2.6-3.6). Although liver-related mortality was particularly high (aHR, 47.6; 95% CI, 16.5-137.4), liver disease accounted for only 10% of deaths in BCS. The most common cause of death was cardiovascular disease (aHR, 2.2; 95% CI, 1.7-2.9).Patients with BCS in Sweden had a 3-fold higher risk of death compared with general population reference individuals. Although mortality from liver diseases was high in relative terms, most patients died from cardiovascular causes.
Efficacy of second CAR-T (CART2) infusion limited by poor CART expansion and antigen modulation
Authors: Elizabeth M Holland, John C Molina, Kniya Dede, Daniel Moyer, Ting Zhou, Constance M Yuan, Hao-Wei Wang, Maryalice Stetler-Stevenson, Crystal Mackall, Terry J Fry, Sandhya Panch, Steven Highfill, David Stroncek, Lauren Little, Daniel W Lee, Haneen Shalabi, Bonnie Yates, Nirali Shah
Journal: Journal for ImmunoTherapy of Cancer (2022)

Chimeric antigen receptor T-cells (CART) are active in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), but relapse remains a substantial challenge. Reinfusion with the same CART product (CART2) in patients with suboptimal response or antigen positive relapse following first infusion (CART1) represents a potential treatment strategy, though early experiences suggest limited efficacy of CART2 with CD19 targeting. We report on our experience with CART2 across a host of novel CAR T-cell trials. This was a retrospective review of children and young adults with B-ALL who received reinfusion with an anti-CD19, anti-CD22, or anti-CD19/22 CART construct on one of 3 CAR T-cells trials at the National Cancer Institute (NCT01593696, NCT02315612, NCT0344839) between July 2012 and January 2021. All patients received lymphodepletion (LD) pre-CART (standard LD: 75 mg/m2 fludarabine, 900 mg/m2 cyclophosphamide; or intensified LD: 120 mg/m2 fludarabine, 1200 mg/m2 cyclophosphamide). Primary objectives were to describe response to and toxicity of CART2. Indication for CART2, impact of LD intensity, and CAR T-cell expansion and leukemia antigen expression between CART infusions was additionally evaluated. Eighteen patients proceeded to CART2 due to persistent (n=7) or relapsed antigen positive disease (n=11) following CART1. Seven of 18 (38.9%) demonstrated objective response (responders) to CART2: 5 achieved a minimal residual disease (MRD) negative CR, 1 had persistent MRD level disease, and 1 showed a partial remission, the latter with eradication of antigen positive disease and emergence of antigen negative B-ALL. Responders included four patients who had not achieved a CR with CART1. Limited cytokine release syndrome was seen following CART2. Peripheral blood CART1 expansion was higher than CART2 expansion (p=0.03). Emergence of antigen negative/dim B-ALL in 6 (33.3%) patients following CART2 contributed to lack of CR. Five of seven (71.4%) responders received intensified LD pre-CART2, which corresponded with higher CART2 expansion than in those receiving standard LD (p=0.029). Diminished CAR T-cell expansion and antigen downregulation/loss impeded robust responses to CART2. A subset of patients, however, may derive benefit from CART2 despite suboptimal response to CART1. Intensified LD may be one strategy to augment CART2 responses, though further study of factors associated with CART2 response, including serial monitoring of antigen expression, is warranted.
Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver
Authors: Wenshu Tang, Jingying Zhou, Weiqin Yang, Yu Feng, Haoran Wu, Myth T. S. Mok, Lingyun Zhang, Zhixian Liang, Xiaoyu Liu, Zhewen Xiong, Xuezhen Zeng, Jing Wang, Jiahuan Lu, Jingqing Li, Hanyong Sun, Xiaoyu Tian, Philip Chun Yeung, Yong Hou, Heung Man Lee, Candice C. H. Lam, Howard H. W. Leung, Anthony W. H. Chan, Ka Fai To, John Wong, Paul B. S. Lai, Kelvin K. C. Ng, Simon K. H. Wong, Vincent W. S. Wong, Alice P. S. Kong, Joseph J. Y. Sung, Alfred S. L. Cheng
Journal: Cellular and Molecular Immunology (2022)
<i>Notes from the Field:</i> Increase in Drug Overdose Deaths Among Hispanic or Latino Persons — Nevada, 2019–2020
Authors: Shawn A. Thomas, Amanda T. Dinwiddie, Elyse Monroy
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Reports have documented national and state-level increases in drug overdose-related emergency department visits, emergency medical services incidents, and deaths among racial and ethnic minority groups in the United States during 2020 amid the COVID-19 pandemic (1-3).In June 2021, the Nevada Department of Health and Human Services reported an increase in drug overdose deaths during 2020 among Hispanic or Latino (Hispanic) persons, who make up approximately one third of Nevada's population (4).To better understand this increase, investigators analyzed 2019-2020 State Unintentional Drug Overdose Reporting System (SUDORS) data.*SUDORS is a CDC surveillance system containing detailed information on death scene investigations, toxicology, and other risk factors associated with fatal drug overdoses of unintentional or undetermined intent.Hispanic persons were identified through the SUDORS ethnicity variable, which considers persons with Mexican, Puerto Rican, Cuban, Central or South American, or other Spanish culture or origin as Hispanic, regardless of race.Chi-square pairwise comparisons with Bonferroni adjustment were used to assess differences between 2019 and 2020 in characteristics and circumstances for all overdose deaths and for those among Hispanic persons (5).From 2019 to 2020, drug overdose deaths among all races and ethnicities in Nevada increased 54.5% (from 510 to 788), compared with 119.7% (from 66 to 145) among Hispanic persons (Table ).By sex and age group, the highest percentage increases occurred among males (overall = 6.9%;Hispanic persons = 6.2%) and those aged <25 years (overall = 77.6%;Hispanic persons = 86.2%).During 2020, the proportions of Hispanic decedents who were male (77.2%) and those aged <25 years (28.3%) were higher than overall proportions (68.3% male; 13.5% aged <25 years).From 2019 to 2020, the proportion * SUDORS is a CDC surveillance system funded through Overdose Data to Action (OD2A) that supports 48 jurisdictions to collect and abstract data on unintentional and undetermined intent drug overdose deaths from death certificates and medical examiner or coroner reports (e.g., scene findings, autopsy reports,
Does Circulating Tumor DNA Measure Up to Prostate-Specific Antigen?
Authors: Tomi Jun, William K. Oh
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Cardiovascular outcomes in patients with chronic kidney disease and COVID-19: a multi-regional data-linkage study
Authors: Emilie J. Lambourg, Peter J. Gallacher, Robert W. Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D. Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell
Journal: European Respiratory Journal (2022)

Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 years; 58.1% women; 15.9% CKD; 10.1% COVID-19 positive) in Cohort 1 and 50 060 patients (mean±sd age 63±20 years; 62.0% women; 16.4% CKD; 9.1% COVID-19 positive) in Cohort 2. In CKD patients, COVID-19 increased the risk of cardiovascular death by more than two-fold within 30 days (cause-specific hazard ratio (csHR) meta-estimate 2.34, 95% CI 1.83-2.99) and by 57% at the end of study follow-up (csHR meta-estimate 1.57, 95% CI 1.31-1.89). Similarly, the risk of all-cause death in COVID-19 positive versus negative CKD patients was greatest within 30 days (HR 4.53, 95% CI 3.97-5.16). Compared with patients without CKD, those with CKD had a higher risk of testing positive (11.5% versus 9.3%). Following a positive test, CKD patients had higher rates of cardiovascular death (11.1% versus 2.7%), cardiovascular complications and cardiovascular hospitalisations (7.1% versus 3.3%) than those without CKD.COVID-19 increases the risk of cardiovascular and all-cause death in CKD patients, especially in the short-term. CKD patients with COVID-19 are also at a disproportionate risk of cardiovascular complications than those without CKD.
Capture Rate of V(D)J Sequencing for Minimal Residual Disease Detection in Multiple Myeloma
Authors: Malin Hultcrantz, Even H. Rustad, Venkata Yellapantula, Allison Jacob, Theresia Akhlaghi, Neha Korde, Sham Mailankody, Alexander M. Lesokhin, Hani Hassoun, Eric L. Smith, Oscar B. Lahoud, Heather J. Landau, Gunjan L. Shah, Michael Scordo, David J. Chung, Sergio Giralt, Elli Papaemmanuil, Ola Landgren
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Minimal residual disease (MRD) negativity is a strong predictor for outcome in multiple myeloma. To assess V(D)J clonotype capture using the updated Adaptive next-generation sequencing (NGS) MRD assay in a clinical setting, we analyzed baseline and follow-up samples from patients with multiple myeloma who achieved deep clinical responses. Experimental Design: A total of 159 baseline and 31 follow-up samples from patients with multiple myeloma were sequenced using the NGS MRD assay. Baseline samples were also sequenced using a targeted multiple myeloma panel (myTYPE). We estimated ORs with 95% confidence intervals (CI) for clonotypes detection using logistic regression. Results: The V(D)J clonotype capture rate was 93% in baseline samples with detectable genomic aberrations, indicating presence of tumor DNA, assessed through myTYPE. myTYPE-positive samples had significantly higher V(D)J clonotype detection rates in univariate (OR, 7.3; 95% CI, 2.8–22.6) and multivariate analysis (OR, 4.4; 95% CI, 1.4–16.9; P = 0.016). Higher disease burden was associated with higher probability of V(D)J clonotype capture, meanwhile no such association was found for age, gender, or type of heavy or light immunoglobulin chain. All V(D)J clonotypes detected at baseline were detected in MRD-positive samples indicating that the V(D)J clonotypes remained stable and did not undergo further rearrangements during follow-up. Of the 31 posttreatment samples, 12 were MRD-negative using the NGS MRD assay. Conclusions: NGS for V(D)J rearrangements in multiple myeloma offers a reliable and sensitive method for MRD tracking with high detection rates in the clinical setting.
Magnesium surface-activated 3D printed porous PEEK scaffolds for in vivo osseointegration by promoting angiogenesis and osteogenesis
Authors: Xinghui Wei, Wenhao Zhou, Zhen Tang, Hao Wu, Yichao Liu, Hui Dong, Ning Wang, Hai Huang, Shusen Bao, Lei Shi, Xiaokang Li, Yufeng Zheng, Zheng Guo
Journal: Bioactive Materials (2022)

Polyetheretherketone (PEEK) has been an alternative material for titanium in bone defect repair, but its clinical application is limited by its poor osseointegration. In this study, a porous structural design and activated surface modification were used to enhance the osseointegration capacity of PEEK materials. Porous PEEK scaffolds were manufactured via fused deposition modeling and a polydopamine (PDA) coating chelated with magnesium ions (Mg2+) was utilized on the surface. After surface modification, the hydrophilicity of PEEK scaffolds was significantly enhanced, and bioactive Mg2+ could be released. In vitro results showed that the activated surface could promote cell proliferation and adhesion and contribute to osteoblast differentiation and mineralization; the released Mg2+ promoted angiogenesis and might contribute to the formation of osteogenic H-type vessels. Furthermore, porous PEEK scaffolds were implanted in rabbit femoral condyles for in vivo evaluation of osseointegration. The results showed that the customized three-dimensional porous structure facilitated vascular ingrowth and bone ingrowth within the PEEK scaffolds. The PDA coating enhanced the interfacial osseointegration of porous PEEK scaffolds and the released Mg2+ accelerated early bone ingrowth by promoting early angiogenesis during the coating degradation process. This study provides an efficient solution for enhancing the osseointegration of PEEK materials, which has high potential for translational clinical applications.
Circulating Tumor DNA Is Associated with Response and Survival in Patients with Advanced Leiomyosarcoma
Authors: Laura M. Madanat-Harjuoja, Kelly Klega, Yao Lu, David S. Shulman, Aaron R. Thorner, Anwesha Nag, William D. Tap, Denise K. Reinke, Lisa Diller, Karla V. Ballman, Suzanne George, Brian D. Crompton
Journal: Clinical Cancer Research (2022)

Abstract Purpose: We sought to determine whether the detection of circulating tumor DNA (ctDNA) in samples of patients undergoing chemotherapy for advanced leiomyosarcoma (LMS) is associated with objective response or survival. Experimental Design: Using ultra–low-passage whole-genome sequencing (ULP-WGS) of plasma cell-free DNA from patients treated on a prospective clinical trial, we tested whether detection of ctDNA evaluated prior to the start of therapy and after two cycles of chemotherapy was associated with treatment response and outcome. Associations between detection of ctDNA and pathologic measures of disease burden were evaluated. Results: We found that ctDNA was detectable by ULP-WGS in 49% patients prior to treatment and in 24.6% patients after two cycles of chemotherapy. Detection of pretreatment ctDNA was significantly associated with a lower overall survival [HR, 1.55; 95% confidence interval (CI), 1.03–2.31; P = 0.03] and a significantly lower likelihood of objective response [odds ratio (OR), 0.21; 95% CI, 0.06–0.59; P = 0.005]. After two cycles of chemotherapy, patients who continued to have detectable levels of ctDNA experienced a significantly worse overall survival (HR, 1.77; 95% CI, 1–3.14; P = 0.05) and were unlikely to experience an objective response (OR, 0.05; 95% CI, 0–0.39; P = 0.001). Conclusions: Our results demonstrate that detection of ctDNA is associated with outcome and objective response to chemotherapy in patients with advanced LMS. These results suggest that liquid biopsy assays could be used to inform treatment decisions by recognizing patients who are likely and unlikely to benefit from chemotherapy. See related commentary by Kasper and Wilky, p. 2480
Scenes From the Children’s Hospital
Authors: Jeffrey G. Howard
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Risk Score to Detect Subclinical Rheumatoid Arthritis–Associated Interstitial Lung Disease
Authors: Pierre‐Antoine Juge, Benjamin Granger, Marie‐Pierre Debray, Esther Ebstein, Fabienne Louis‐Sidney, Joanna Kedra, Tracy J. Doyle, Raphaël Borie, Arnaud Constantin, Bernard Combe, René‐Marc Flipo, Xavier Mariette, Olivier Vittecoq, Alain Saraux, Guillermo Carvajal‐Alegria, Jean Sibilia, Francis Berenbaum, Caroline Kannengiesser, Catherine Boileau, Jeffrey A. Sparks, Bruno Crestani, Bruno Fautrel, Philippe Dieudé
Journal: Arthritis & Rheumatology (2022)

Patients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms; this can be done by screening patients with the use of chest high-resolution computed tomography (HRCT). Our objective was to develop and validate a risk score for patients who have subclinical RA-ILD.
Missing perspective: Marginalized groups in the social psychological study of social disparities
Authors: Jes L. Matsick, Flora Oswald, Mary Kruk
Journal: Behavioral and Brain Sciences (2022)

Abstract Drawing on interdisciplinary, feminist insights, we encourage social psychologists to embrace the active participation of marginalized groups in social disparities research. We explain (1) how the absence of marginalized groups' perspectives in research presents a serious challenge to understanding intergroup dynamics and concomitant disparities, and (2) how their inclusion could assuage some of social psychology's “fatal flaws.”